gallo et al (iser 2012)

Emiliano S. Lopez , Oscar J. Croxatto, Juan E. Gallo

Facultad de Ciencias Biomédicas, Universidad Austral; Oftalmologia, Hospital Universitario Austral , Pilar- Buenos Aires ; Patologia Ocular, Fundación Oftalmológica Argentina "Jorge

Malbran", Buenos Aires, Argentina.

SURAMAB

- EP 2186529; granted 28 March 2012.

- US Patent pending.

BevacizumabBevacizumab

SuraminSuramin

We have previously shown that Suramab, a novel pharmaceutical compound, has antiangiogenic properties.

ES Lopez , MM Rizzo, JO Croxatto , G Mazzolini , JE Gallo. Suramab, a novel antiangiogenic agent, reduces tumor growth and corneal neovascularization. Cancer Chemother Pharmacol 2011; 67:723–728

To analyse the role of VEGF, bFGF, LYVE-1 and P2X2 in the antiangiogenic mechanism of suramab in a rabbit model of corneal neovascularization.

9 Rabbits 9 Rabbits 9 Rabbits

Photographs d9 d15 d21 d35

Anesthesia filter disc (7mm) Na(OH) 1M (1min) Wash SB

-L. David Ormerod. Standard Models of Corneal Injury Using Alcali-Inmersed filter discs. Investigative Ophthalmology & Visual Science, Vol. 30, Nº. 10, October 1989.

Suramab Bevacizumab Control

DAY 9

DAY15

DAY 35

CLINICAL FOLLOW-UP

Rabbits treated with Suramab Suramab showed a lower neovessel index than that seen in controls at 35 days (T student, p<0.0001).

Suramab Suramab had a greater antiangiogenic effect than that seen in animals treated with Bevacizumab Bevacizumab (T student, p<0.02).

Suramab Control

CONTROL TREATED GROUPS

SuramabControl Bevacizumab

S C B

42kDa

43kDa

VEGF

ACTIN

SURAMABSURAMAB BEVACIZUMAB CONTROLBEVACIZUMAB CONTROL

S C B

LYVE-140 kD

ACTIN 43 kD

Bevacizumab SuramabControl

50kD

43kD

P2X2

ACTIN

C S B

B C S

B C S

bFGF

ACTIN

43 kD

19 kD

Western Blot

- Suramab has a strong antiangiogenic effect.

- VEGF, P2X2, LYVE-1 and bFGF are involved in the antiangiogenic mechanism.

CONCLUSIONS

CONTROL

Clinical evolution

Control S

S+P0

10

20

30

40

50

Groups ( 14 days postinjury)

Are

a o

f N

V (

%)

ControlControl 38.22 35.3 30 29 31 22

SuramabSuramab 19.4 3 6 5 8 9

S+PS+P 5 0 1 2 1 1

Control Suramab+P Suramab

- Drug delivery systems are being currently developed to improve suramab ´s performance in the treatment of corneal and retinal neovascularization.

CONCLUSIONS

THANK YOU!

3 Conejos 3 Conejos 3 Conejos

Control Suramina EV Bevacizumab

DIA 9

DIA 35

Evolución clínicaEvolución clínica

Días post-lesión

INV

pro

med

ios

P407/P188 VehículoPolímero% (w/w)

T gel I (°C)

T gel II (°C)

Viscosidad a 35°C (Pas)

(24/20)%w/w

NaCl 0.9% 26,4 27,9 14100

NaCl 0.9%0,5 (Chitosan)

24,8 26,4 17800

NaCl 0.9% 0,25 (Hialuronato de Sodio)

25,3 27,9 14100

1,00E-01

1,00E+00

1,00E+01

1,00E+02

1,00E+03

1,00E+04

0 5 10 15 20 25 30 35 40 45

Viscosity (Pa.s)

Temperatura °C

P407/P188/NaCl/Chitosan (24/20/0.9/0.5 % w/w)

Poloxamers

Poloxamers-Hialuronato

Poloxamers-Chitosan

Dr. Santiago Palma, Daniela Quinteros. Universidad Nacional de Cordoba